1015 CHAPTER 26 LIPIDS L ipids differ from the other classes of naturally occurring biomolecules (carbohy- drates, proteins, and nucleic acids) in that they are more soluble in non-to-weakly polar solvents (diethyl ether, hexane, dichloromethane) than they are in water. They include a variety of structural types, a collection of which is introduced in this chapter. In spite of the number of different structural types, lipids share a common biosyn- thetic origin in that they are ultimately derived from glucose. During one stage of car- bohydrate metabolism, called glycolysis, glucose is converted to lactic acid. Pyruvic acid is an intermediate. In most biochemical reactions the pH of the medium is close to 7. At this pH, carboxylic acids are nearly completely converted to their conjugate bases. Thus, it is common practice in biological chemistry to specify the derived carboxylate anion rather than the carboxylic acid itself. For example, we say that glycolysis leads to lactate by way of pyruvate. Pyruvate is used by living systems in a number of different ways. One pathway, the one leading to lactate and beyond, is concerned with energy storage and production. This is not the only pathway available to pyruvate, however. A signifi cant fraction of it is converted to acetate for use as a starting material in the biosynthesis of more com- plex substances, especially lipids. By far the major source of lipids is biosynthesis via acetate and this chapter is organized around that theme. Well begin by looking at the reaction in which acetate (two carbons) is formed from pyruvate (three carbons). C6H12O6 Glucose O CH3CCO2H Pyruvic acid OH CH3CHCO2H Lactic acid BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website 1016CHAPTER TWENTY-SIXLipids 26.1ACETYL COENZYME A The form in which acetate is used in most of its important biochemical reactions is acetyl coenzyme A (Figure 26.1a). Acetyl coenzyme A is a thioester (Section 20.12). Its for- mation from pyruvate involves several steps and is summarized in the overall equation: All the individual steps are catalyzed by enzymes. NAD?(Section 15.11) is required as an oxidizing agent, and coenzyme A (Figure 26.1b) is the acetyl group acceptor. Coen- zyme A is a thiol; its chain terminates in a sulfhydryl (SH) group. Acetylation of the sulfhydryl group of coenzyme A gives acetyl coenzyme A. As we saw in Chapter 20, thioesters are more reactive than ordinary esters toward nucleophilic acyl substitution. They also contain a greater proportion of enol at equilib- rium. Both properties are apparent in the properties of acetyl coenzyme A. In some reac- tions it is the carbonyl group of acetyl coenzyme A that reacts; in others it is the ?- carbon atom. O CH3CSCoA Acetyl coenzyme A CH2 OH CSCoA Enol form reaction at ? carbon nucleophilic acyl substitution HYE? E O CH2CSCoA ? H?Y O CH3C? HSCoA OO CH3CCOH Pyruvic acid O CH3CSCoA Acetyl coenzyme A CoASH Coenzyme A ?NAD? Oxidized form of nicotinamide adenine dinucleotide NADH Reduced form of nicotinamide adenine dinucleotide CO2 Carbon dioxide H? Proton ? HOPO HO SR CH3 NH2 O N N N N O N O N HH OH O OO PP OHHO OO CH3 O HO (a) (b) Acetyl coenzyme A (abbreviation: CH 3 O Coenzyme A (abbreviation: CoASH) R ? H R ? CCH O CSCoA) 3 Coenzyme A was isolated and identifi ed by Fritz Lip- mann, an American bio- chemist. Lipmann shared the 1953 Nobel Prize in physiol- ogy or medicine for this work. FIGURE 26.1 Structures of (a) acetyl coenzyme A and (b) coenzyme A. BackForwardMain MenuTOCStudy Guide TOCStudent OLCMHHE Website 26.2Fats, Oils, and Fatty Acids1017 Well see numerous examples of both reaction types in the following sections. Keep in mind that in vivo reactions (reactions in living systems) are enzyme-catalyzed and occur at rates that are far greater than when the same transformations are carried out in vitro (“in glass”) in the absence of enzymes. In spite of the rapidity with which enzyme-catalyzed reactions take place, the nature of these transformations is essentially the same as the fundamental processes of organic chemistry described throughout this text. Fats are one type of lipid. They have a number of functions in living systems, including that of energy storage. Although carbohydrates serve as a source of readily available energy, an equal weight of fat delivers over twice the amount of energy. It is more effi cient for an organism to store energy in the form of fat because it requires less mass than storing the same amount of energy in carbohydrates or proteins. How living systems convert acetate to fats is an exceedingly complex story, one that is well understood in broad outline and becoming increasingly clear in detail as well. We will examine several aspects of this topic in the next few sections, focusing mostly on its structural and chemical features. 26.2FATS, OILS, AND FATTY ACIDS Fats and oils are naturally occurring mixtures of triacylglycerols, also called triglyc- erides. They differ in that fats are